The objective of this study is to identify and specify in human subjects changes in chromosomal deoxyribonucleic acid (DNA), caused by opiates, their antagonists or replacements, which may have mutagenic, carcinogenic or pathological effects. A battery of tests stress systems has been assembled to detect stable and unstable chromosome alterations at the structural and molecular levels as well as defects at the metabolic level of the DNA repair processes. The use of stress by such known mutagenic agents as far ultraviolet light, ethylmethylsulfonate, 8-methoxylpsoralennear ultraviolet, mitomycin C, and bromouridine deoxyribose-near ultraviolet light, was instituted to mimic possible mutagenic effects of environmental agents, and to measure the differential response of lymphocytes from opiate addicts and those of control subjects to such induced mutations. The response of the cells to these agents is quantitated at the cytological level in terms of morphologically identifiable chromosomal abberations and changes in the frequency of sister chromatid exchanges, and at the biochemical level in terms of several types of DNA repair including excision, photoreactivation and post-replication repair. Correlation of these measurements should enable us to identify even subtle genetic alterations which may result from addiction to drugs of abuse.